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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Jul;81(14):4510–4514. doi: 10.1073/pnas.81.14.4510

Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2.

J D Fingeroth, J J Weis, T F Tedder, J L Strominger, P A Biro, D T Fearon
PMCID: PMC345620  PMID: 6087328

Abstract

Identity of the Epstein-Barr virus (EBV) receptor with the complement receptor type 2 (CR2) was established in three sets of experiments using the monoclonal antibodies, HB-5 and anti-B2, which recognize a Mr 145,000 B-lymphocyte membrane protein that is CR2. First, the rank order for binding of fluoresceinated EBV to four lymphoblastoid cell lines (SB, JY, Raji, and Molt-4) was identical to the rank order for binding of HB-5 and anti-B2 by analytical flow cytometry. Second, pretreatment of cells with HB-5 followed by treatment with goat F(ab')2 fragments to mouse IgG blocked binding of fluoresceinated EBV on SB, a B-lymphoblastoid cell line. Virus attachment was not inhibited by HB-5 alone, second antibody alone, rabbit anti-C3b receptor, or UPC10 (an irrelevant monoclonal antibody). Third, transfer of CR2 from SB to protein A-bearing Staphylococcus aureus particles, to which HB-5 had been absorbed, conferred on them the specific ability to bind 125I-labeled EBV. We conclude that CR2 is the EBV receptor of human B lymphocytes.

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Selected References

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  1. Arnaout M. A., Todd R. F., 3rd, Dana N., Melamed J., Schlossman S. F., Colten H. R. Inhibition of phagocytosis of complement C3- or immunoglobulin G-coated particles and of C3bi binding by monoclonal antibodies to a monocyte-granulocyte membrane glycoprotein (Mol). J Clin Invest. 1983 Jul;72(1):171–179. doi: 10.1172/JCI110955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnstable C. J., Bodmer W. F., Brown G., Galfre G., Milstein C., Williams A. F., Ziegler A. Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis. Cell. 1978 May;14(1):9–20. doi: 10.1016/0092-8674(78)90296-9. [DOI] [PubMed] [Google Scholar]
  3. Beller D. I., Springer T. A., Schreiber R. D. Anti-Mac-1 selectively inhibits the mouse and human type three complement receptor. J Exp Med. 1982 Oct 1;156(4):1000–1009. doi: 10.1084/jem.156.4.1000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bhan A. K., Nadler L. M., Stashenko P., McCluskey R. T., Schlossman S. F. Stages of B cell differentiation in human lymphoid tissue. J Exp Med. 1981 Sep 1;154(3):737–749. doi: 10.1084/jem.154.3.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bird A. G., Britton S. A live human B-cell activator operating in isolation of other cellular influences. Scand J Immunol. 1979;9(6):507–510. doi: 10.1111/j.1365-3083.1979.tb03278.x. [DOI] [PubMed] [Google Scholar]
  6. Bokisch V. A., Müller-Eberhard H. J., Cochrane C. G. Isolation of a fragment (C3a) of the third component of human complement containing anaphylatoxin and chemotactic activity and description of an anaphylatoxin inactivator of human serum. J Exp Med. 1969 May 1;129(5):1109–1130. doi: 10.1084/jem.129.5.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carlo J. R., Ruddy S., Studer E. J., Conrad D. H. Complement receptor binding of C3b-coated cells treated with C3b inactivator, beta 1H globulin and trypsin. J Immunol. 1979 Aug;123(2):523–528. [PubMed] [Google Scholar]
  8. Cooper N. R. Immune adherence by the fourth component of complement. Science. 1969 Jul 25;165(3891):396–398. doi: 10.1126/science.165.3891.396. [DOI] [PubMed] [Google Scholar]
  9. Daha M. R., Bloem A. C., Ballieux R. E. Immunoglobulin production by human peripheral lymphocytes induced by anti-C3 receptor antibodies. J Immunol. 1984 Mar;132(3):1197–1201. [PubMed] [Google Scholar]
  10. Dobson N. J., Lambris J. D., Ross G. D. Characteristics of isolated erythrocyte complement receptor type one (CR1, C4b-C3b receptor) and CR1-specific antibodies. J Immunol. 1981 Feb;126(2):693–698. [PubMed] [Google Scholar]
  11. Dolyniuk M., Pritchett R., Kieff E. Proteins of Epstein-Barr virus. I. Analysis of the polypeptides of purified enveloped Epstein-Barr virus. J Virol. 1976 Mar;17(3):935–949. doi: 10.1128/jvi.17.3.935-949.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dykman T. R., Cole J. L., Iida K., Atkinson J. P. Structural heterogeneity of the C3b/C4b receptor (Cr 1) on human peripheral blood cells. J Exp Med. 1983 Jun 1;157(6):2160–2165. doi: 10.1084/jem.157.6.2160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Eden A., Miller G. W., Nussenzweig V. Human lymphocytes bear membrane receptors for C3b and C3d. J Clin Invest. 1973 Dec;52(12):3239–3242. doi: 10.1172/JCI107525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Einhorn L., Steinitz M., Yefenof E., Ernberg I., Bakacs T., Klein G. Epstein-Barr virus (EBV) receptors, complement receptors, and EBV infectibility of different lymphocyte fractions of human peripheral blood. II. Epstein-Barr virus studies. Cell Immunol. 1978 Jan;35(1):43–58. doi: 10.1016/0008-8749(78)90125-9. [DOI] [PubMed] [Google Scholar]
  15. Fearon D. T. Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, B lymphocyte, and monocyte. J Exp Med. 1980 Jul 1;152(1):20–30. doi: 10.1084/jem.152.1.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
  17. Gaither T. A., Magrath I. T., Berger M., Hammer C. H., Novikovs L., Santaella M., Frank M. M. Complement receptor expression by neoplastic and normal human cells. J Immunol. 1983 Aug;131(2):899–905. [PubMed] [Google Scholar]
  18. Gelfand M. C., Frank M. M., Green I. A receptor for the third component of complement in the human renal glomerulus. J Exp Med. 1975 Oct 1;142(4):1029–1034. doi: 10.1084/jem.142.4.1029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hutt-Fletcher L. M., Fowler E., Lambris J. D., Feighny R. J., Simmons J. G., Ross G. D. Studies of the Epstein Barr virus receptor found on Raji cells. II. A comparison of lymphocyte binding sites for Epstein Barr virus and C3d. J Immunol. 1983 Mar;130(3):1309–1312. [PubMed] [Google Scholar]
  20. Iida K., Nadler L., Nussenzweig V. Identification of the membrane receptor for the complement fragment C3d by means of a monoclonal antibody. J Exp Med. 1983 Oct 1;158(4):1021–1033. doi: 10.1084/jem.158.4.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Inada S., Brown E. J., Gaither T. A., Hammer C. H., Takahashi T., Frank M. M. C3d receptors are expressed on human monocytes after in vitro cultivation. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2351–2355. doi: 10.1073/pnas.80.8.2351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jondal M., Klein G., Oldstone M. B., Bokish V., Yefenof E. Surface markers on human B and T lymphocytes. VIII. Association between complement and Epstein-Barr virus receptors on human lymphoid cells. Scand J Immunol. 1976;5(4):401–410. doi: 10.1111/j.1365-3083.1976.tb00294.x. [DOI] [PubMed] [Google Scholar]
  23. Jønsson V., Wells A., Klein G. Receptors for the complement C3d component and the Epstein-Barr virus are quantitatively coexpressed on a series of B-cell lines and their derived somatic cell hybrids. Cell Immunol. 1982 Sep 15;72(2):263–276. doi: 10.1016/0008-8749(82)90474-9. [DOI] [PubMed] [Google Scholar]
  24. Khelifa R., Menezes J. Use of fluoresceinated Epstein-Barr virus to study Epstein-Barr virus-lymphoid cell interactions. J Virol. 1982 Feb;41(2):649–656. doi: 10.1128/jvi.41.2.649-656.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kirchner H., Tosato G., Blaese R. M., Broder S., Magrath I. T. Polyclonal immunoglobulin secretion by human B lymphocytes exposed to Epstein-Barr virus in vitro. J Immunol. 1979 Apr;122(4):1310–1313. [PubMed] [Google Scholar]
  26. Lozzio C. B., Lozzio B. B. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 1975 Mar;45(3):321–334. [PubMed] [Google Scholar]
  27. Magrath I., Freeman C., Santaella M., Gadek J., Frank M., Spiegel R., Novikovs L. Induction of complement receptor expression in cell lines derived from human undifferentiated lymphomas. II. Characterization of the induced complement receptors and demonstration of the simultaneous induction of EBV receptor. J Immunol. 1981 Sep;127(3):1039–1043. [PubMed] [Google Scholar]
  28. Medof M. E., Iida K., Mold C., Nussenzweig V. Unique role of the complement receptor CR1 in the degradation of C3b associated with immune complexes. J Exp Med. 1982 Dec 1;156(6):1739–1754. doi: 10.1084/jem.156.6.1739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Miller G., Lipman M. Release of infectious Epstein-Barr virus by transformed marmoset leukocytes. Proc Natl Acad Sci U S A. 1973 Jan;70(1):190–194. doi: 10.1073/pnas.70.1.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Minowada J., Onuma T., Moore G. E. Rosette-forming human lymphoid cell lines. I. Establishment and evidence for origin of thymus-derived lymphocytes. J Natl Cancer Inst. 1972 Sep;49(3):891–895. [PubMed] [Google Scholar]
  31. Nadler L. M., Stashenko P., Hardy R., van Agthoven A., Terhorst C., Schlossman S. F. Characterization of a human B cell-specific antigen (B2) distinct from B1. J Immunol. 1981 May;126(5):1941–1947. [PubMed] [Google Scholar]
  32. PULVERTAFT J. V. A STUDY OF MALIGNANT TUMOURS IN NIGERIA BY SHORT-TERM TISSUE CULTURE. J Clin Pathol. 1965 May;18:261–273. doi: 10.1136/jcp.18.3.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Perlmann H., Perlmann P., Schreiber R. D., Müller-Eberhard H. J. Interaction of target cell-bound C3bi and C3d with human lymphocyte receptors. Enhancement of antibody-mediated cellular cytotoxicity. J Exp Med. 1981 Jun 1;153(6):1592–1603. doi: 10.1084/jem.153.6.1592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ross G. D., Lambris J. D. Identification of a C3bi-specific membrane complement receptor that is expressed on lymphocytes, monocytes, neutrophils, and erythrocytes. J Exp Med. 1982 Jan 1;155(1):96–110. doi: 10.1084/jem.155.1.96. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ross G. D., Polley M. J., Rabellino E. M., Grey H. M. Two different complement receptors on human lymphocytes. One specific for C3b and one specific for C3b inactivator-cleaved C3b. J Exp Med. 1973 Oct 1;138(4):798–811. doi: 10.1084/jem.138.4.798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Royston I., Smith R. W., Buell D. N., Huang E. S., Pagano J. S. Autologous human B and T lymphoblastoid cell lines. Nature. 1974 Oct 25;251(5477):745–746. doi: 10.1038/251745a0. [DOI] [PubMed] [Google Scholar]
  37. Schwaber J. F., Klein G., Ernberg I., Rosen A., Lazarus H., Rosen F. S. Deficiency of Epstein-Barr virus (EBV) receptors on B lymphocytes from certain patients with common varied agammaglobulinemia. J Immunol. 1980 May;124(5):2191–2196. [PubMed] [Google Scholar]
  38. Simmons J. G., Hutt-Fletcher L. M., Fowler E., Feighny R. J. Studies of the Epstein-Barr virus receptor found on Raji cells. I. Extraction of receptor and preparation of anti-receptor antibody. J Immunol. 1983 Mar;130(3):1303–1308. [PubMed] [Google Scholar]
  39. Terhorst C., Parham P., Mann D. L., Strominger J. L. Structure of HLA antigens: amino-acid and carbohydrate compositions and NH2-terminal sequences of four antigen preparations. Proc Natl Acad Sci U S A. 1976 Mar;73(3):910–914. doi: 10.1073/pnas.73.3.910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Trowbridge I. S., Hyman R., Klein G. Human B cell line deficient in the expression of B cell-specific glycoproteins (GP 27,35). Eur J Immunol. 1977 Sep;7(9):640–645. doi: 10.1002/eji.1830070912. [DOI] [PubMed] [Google Scholar]
  41. Weigle W. O., Goodman M. G., Morgan E. L., Hugli T. E. Regulation of immune response by components of the complement cascade and their activated fragments. Springer Semin Immunopathol. 1983;6(2-3):173–194. doi: 10.1007/BF00205872. [DOI] [PubMed] [Google Scholar]
  42. Weis J. J., Tedder T. F., Fearon D. T. Identification of a 145,000 Mr membrane protein as the C3d receptor (CR2) of human B lymphocytes. Proc Natl Acad Sci U S A. 1984 Feb;81(3):881–885. doi: 10.1073/pnas.81.3.881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wells A., Koide N., Stein H., Gerdes J., Klein G. The Epstein-Barr virus receptor is distinct from the C3 receptor. J Gen Virol. 1983 Feb;64(Pt 2):449–453. doi: 10.1099/0022-1317-64-2-449. [DOI] [PubMed] [Google Scholar]
  44. Wilson J. G., Tedder T. F., Fearon D. T. Characterization of human T lymphocytes that express the C3b receptor. J Immunol. 1983 Aug;131(2):684–689. [PubMed] [Google Scholar]
  45. Wong W. W., Wilson J. G., Fearon D. T. Genetic regulation of a structural polymorphism of human C3b receptor. J Clin Invest. 1983 Aug;72(2):685–693. doi: 10.1172/JCI111018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wright S. D., Rao P. E., Van Voorhis W. C., Craigmyle L. S., Iida K., Talle M. A., Westberg E. F., Goldstein G., Silverstein S. C. Identification of the C3bi receptor of human monocytes and macrophages by using monoclonal antibodies. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5699–5703. doi: 10.1073/pnas.80.18.5699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Yefenof E., Klein G., Jondal M., Oldstone M. B. Surface markers on human B and T-lymphocytes. IX. Two-color immunofluorescence studies on the association between ebv receptors and complement receptors on the surface of lymphoid cell lines. Int J Cancer. 1976 Jun 15;17(6):693–700. doi: 10.1002/ijc.2910170602. [DOI] [PubMed] [Google Scholar]
  48. Yefenof E., Klein G., Kvarnung K. Relationships between complement activation, complement binding, and EBV absorption by human hematopoietic cell lines. Cell Immunol. 1977 Jun 15;31(2):225–233. doi: 10.1016/0008-8749(77)90024-7. [DOI] [PubMed] [Google Scholar]
  49. Yefenof E., Klein G. Membrane receptor stripping confirms the association between EBV receptors and complement receptors on the surface of human B lymphoma lines. Int J Cancer. 1977 Sep 15;20(3):347–352. doi: 10.1002/ijc.2910200305. [DOI] [PubMed] [Google Scholar]

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